A novel superior medication-based chronic disease score predicted all-cause mortality in independent geriatric cohorts.

OBJECTIVES: On the basis of current treatment guidelines, we developed and validated a medication-based chronic disease score (medCDS) and tested its association with all-cause mortality of older outpatients. STUDY DESIGN AND SETTING: Considering the most prevalent chronic diseases in the elderly German population, we compiled a list of evidence-based medicines used to treat these disorders. Based on this list, a score (medCDS) was developed to predict mortality using data of a large longitudinal cohort of older outpatients (training sample; MultiCare Cohort Study). By assessing receiver-operating characteristics (ROC) curves, the performance of medCDS was then confirmed in independent cohorts (ESTHER, KORA-Age) of community-dwelling older patients and compared with already existing medication-based scores and a score using selected anatomical-therapeutic-chemical (ATC) codes. RESULTS: The final medCDS score had an ROC area under the curve (AUC) of 0.73 (95% CI 0.70-0.76). In the validation cohorts, its ROC AUCs were 0.79 (0.76-0.82, KORA-Age) and 0.74 (0.71-0.78, ESTHER), which were superior to already existing medication-based scores (RxRisk, CDS) and scores based on pharmacological ATC code subgroups (ATC3) or age and sex alone (Age&Sex). CONCLUSIONS: A new medCDS, which is based on actual treatment standards, predicts mortality of older outpatients significantly better than already existing scores.

Regional variation of chronic kidney disease in Germany: results from two population-based surveys.

BACKGROUND/AIMS: Due to the increasing prevalence of risk factors for chronic kidney disease (CKD), kidney dysfunction becomes a major public health problem. We investigated the CKD prevalence and determined to what extent the variation of risk factors explains the different CKD prevalence in Germany. METHODS: We analyzed data from 6,054 participants, aged 31 to 82 years, from the Study of Health in Pomerania (SHIP-1) in Northeast Germany and the Cooperative Health Research in the Region of Augsburg (KORA F4) Study in Southern Germany. Regional differences in selected percentiles corresponding to the cutpoints for estimated glomerular filtration rate (eGFR, <60 ml/min per 1.73 m(2)) and albumin-to-creatinine ratio (ACR, ≥30 mg/g) were tested using quantile regression models that adjusted for CKD risk factors. RESULTS: The prevalence of decreased eGFRcreatinine-cystatinC (5.9 vs. 3.1 %, p <0.001) and albuminuria (20.2 vs. 8.8 %, p<0.001) were higher in SHIP-1 than in KORA F4. The differential distribution of risk factors explained 18-21% of the regional differences of decreased eGFRcreatinine-cystatinC and high ACR. CONCLUSIONS: The CKD prevalence is higher in Northeast than in Southern Germany. Differences in the prevalence of risk factors partly explain the higher disease burden of CKD in Northeast than in Southern Germany.

Neighborhood and healthy aging in a German city: distances to green space and senior service centers and their associations with physical constitution, disability, and health-related quality of life.

The composition of the residential environment may have an independent influence on health, especially in older adults. In this cross-sectional study, we examined the associations between proximity to two features of the residential environment (green space and senior service centers) and three aspects of healthy aging (self-rated physical constitution, disability, and health-related quality of life). We included 1711 inhabitants from the city of Augsburg, Germany, aged 65 years or older, who participated in the KORA-Age study conducted in 2008/2009. We calculated the Euclidian distances between each participant's residential address and the nearest green space or senior service center, using a geographic information system. Multilevel logistic regression models were fitted to analyze the associations, controlling for demographic and socioeconomic factors. Contrary to expectations, we did not find clear associations between the distances to the nearest green space or senior service center and any of the examined aspects of healthy aging. The importance of living close to green space may largely depend on the study location. The city of Augsburg is relatively small (about 267,000 inhabitants) and has a high proportion of greenness. Thus, proximity to green space may not be as important as in a densely populated metropolitan area. Moreover, an objectively defined measure of access such as Euclidian distance may not reflect the actual use. Future studies should try to assess the importance of resources of the residential environment not only objectively, but also from the resident's perspective.

Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci.

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10(-11)) and 8q12 (minimum p value 1.82×10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.

Interrogating causal pathways linking genetic variants, small molecule metabolites, and circulating lipids.

BACKGROUND: Emerging technologies based on mass spectrometry or nuclear magnetic resonance enable the monitoring of hundreds of small metabolites from tissues or body fluids. Profiling of metabolites can help elucidate causal pathways linking established genetic variants to known disease risk factors such as blood lipid traits. METHODS: We applied statistical methodology to dissect causal relationships between single nucleotide polymorphisms, metabolite concentrations, and serum lipid traits, focusing on 95 genetic loci reproducibly associated with the four main serum lipids (total-, low-density lipoprotein-, and high-density lipoprotein- cholesterol and triglycerides). The dataset used included 2,973 individuals from two independent population-based cohorts with data for 151 small molecule metabolites and four main serum lipids. Three statistical approaches, namely conditional analysis, Mendelian randomization, and structural equation modeling, were compared to investigate causal relationship at sets of a single nucleotide polymorphism, a metabolite, and a lipid trait associated with one another. RESULTS: A subset of three lipid-associated loci (FADS1, GCKR, and LPA) have a statistically significant association with at least one main lipid and one metabolite concentration in our data, defining a total of 38 cross-associated sets of a single nucleotide polymorphism, a metabolite and a lipid trait. Structural equation modeling provided sufficient discrimination to indicate that the association of a single nucleotide polymorphism with a lipid trait was mediated through a metabolite at 15 of the 38 sets, and involving variants at the FADS1 and GCKR loci. CONCLUSIONS: These data provide a framework for evaluating the causal role of components of the metabolome (or other intermediate factors) in mediating the association between established genetic variants and diseases or traits.

Are psychosocial stressors associated with the relationship of alcohol consumption and all-cause mortality?

BACKGROUND: Several studies have shown a protective association of moderate alcohol intake with mortality. However, it remains unclear whether this relationship could be due to misclassification confounding. As psychosocial stressors are among those factors that have not been sufficiently controlled for, we assessed whether they may confound the relationship between alcohol consumption and all-cause mortality. METHODS: Three cross-sectional MONICA surveys (conducted 1984-1995) including 11,282 subjects aged 25-74 years were followed up within the framework of KORA (Cooperative Health Research in the Region of Augsburg), a population-based cohort, until 2002. The prevalences of diseases as well as of lifestyle, clinical and psychosocial variables were compared in different alcohol consumption categories. To assess all-cause mortality risks, hazard ratios (HRs) were estimated by Cox proportional hazards models which included lifestyle, clinical and psychosocial variables. RESULTS: Diseases were more prevalent among non-drinkers than among drinkers: Moreover, non-drinkers showed a higher percentage of an unfavourable lifestyle and were more affected with psychosocial stressors at baseline. Multivariable-adjusted HRs for moderate alcohol consumption versus no consumption were 0.74 (95% confidence interval (CI): 0.58-0.94) in men and 0.87 (95% CI: 0.66-1.16) in women. In men, moderate drinkers had a significantly lower all-cause mortality risk than non-drinkers or heavy drinkers (p=0.002) even after multivariable adjustment. In women, moderate alcohol consumption was not associated with lowered risk of death from all causes. CONCLUSIONS: The present study confirmed the impact of sick quitters on mortality risk, but failed to show that the association between alcohol consumption and mortality is confounded by psychosocial stressors.

Diastrophic dysplasia sulfate transporter (SLC26A2) is expressed in the adrenal cortex and regulates aldosterone secretion.

Elucidation of the molecular mechanisms leading to autonomous aldosterone secretion is a prerequisite to define potential targets and biomarkers in the context of primary aldosteronism. After a genome-wide association study with subjects from the population-based Cooperative Health Research in the Region of Augsburg F4 survey, we observed a highly significant association (P=6.78×10(-11)) between the aldosterone to renin ratio and a locus at 5q32. Hypothesizing that this locus may contain genes of relevance for the pathogenesis of primary aldosteronism, we investigated solute carrier family 26 member 2 (SLC26A2), a protein with known transport activity for sulfate and other cations. Within murine tissues, adrenal glands showed the highest expression levels for SLC26A2, which was significantly downregulated on in vivo stimulation with angiotensin II and potassium. SLC26A2 expression was found to be significantly lower in aldosterone-producing adenomas in comparison with normal adrenal glands. In adrenocortical NCI-H295R cells, specific knockdown of SLC26A2 resulted in a highly significant increase in aldosterone secretion. Concomitantly, expression of steroidogenic enzymes, as well as upstream effectors including transcription factors such as NR4A1, CAMK1, and intracellular Ca(2+) content, was upregulated in knockdown cells. To substantiate further these findings in an SLC26A2 mutant mouse model, aldosterone output proved to be increased in a sex-specific manner. In summary, these findings point toward a possible effect of SLC26A2 in the regulation of aldosterone secretion potentially involved in the pathogenesis of primary aldosteronism.

Association between anemia and falls in community-dwelling older people: cross-sectional results from the KORA-Age study.

BACKGROUND: Falls and fractures are among the principal causes of disability, and mortality of older people. Therefore, identifying treatable risk factors for falls in this population is very important. Here we evaluate the association between anemia and falls in community-dwelling people aged 65 years and older. METHODS: In 2009 967 community-dwelling people aged 65 years and older were included as part of the KORA-Age study. History of falls was assessed via questions derived from the National Health and Nutrition Examination Survey questionnaire. A non-fasting venous blood sample was obtained from all study participants. Anemia was defined as a hemoglobin level below 12 g/dL in women and below 13 g/dL in men according to the WHO criteria. Different logistic regression models were computed including relevant confounders such as sex, age, and disability to estimate Odds Ratios (OR) for falls. RESULTS: In the total sample there was no significant association between anemia and falls neither in the unadjusted (OR 1.35; 95% CI 0.87-2.09) nor in the multivariable-adjusted models (OR 1.06; 95% CI 0.66-1.70). The association between continuous hemoglobin levels and falls was significant in the unadjusted model (OR per 1 SD decrease 1.36; 95% CI 1.14-1.64), but after adjustment for age and sex the association was attenuated and lost its significance (OR 1.13; 95% CI 0.92-1.38). In age- and sex-stratified analyses, no significant associations between anemia or hemoglobin levels and falls could be found. However, in joint analysis in the total sample a significantly, more than two-fold increased risk was observed after multivariable adjustment in persons with anemia and disability (OR 2.10; 95% CI 1.12-3.93) in comparison to persons without anemia and disability. CONCLUSIONS: In the present study we have not found an independent association between hemoglobin levels or anemia and falls in older people from the general population. Because there was an additive effect of anemia and disability on the occurrence of falls, blood count should be measured in disabled older men and women to identify persons, who are at particular high risk for falls.

Age- and sex-specific reference intervals across life span for insulin-like growth factor binding protein 3 (IGFBP-3) and the IGF-I to IGFBP-3 ratio measured by new automated chemiluminescence assays.

CONTEXT: Measurement of IGF-binding protein-3 (IGFBP-3) can aid the diagnosis of GH-related diseases. Furthermore, epidemiological studies suggest that IGFBP-3 and the molar IGF-I to IGFBP-3 ratio are associated with clinical end points like cancer or cardiovascular disease. However, their clinical use is limited by the lack of validated reference intervals. OBJECTIVE: The objective of the study was the establishment of age- and sex-specific reference intervals for IGFBP-3 and the molar IGF-I to IGFBP-3 ratio by newly developed automated immunoassays. SETTING: This was a multicenter study with samples from 11 cohorts from the United States, Canada, and Europe. PARTICIPANTS: A total of 14 970 healthy subjects covering all ages from birth to senescence participated in the study. MAIN OUTCOME MEASURES: Concentrations of IGFBP-3 and the IGF-I to IGFBP-3 ratio as determined by the IDS iSYS IGF-I and IGFBP-3 assays were measured. RESULTS: Both the concentration of IGFBP-3 and the IGF-I to IGFBP-3 ratio are mainly determined by age. IGFBP-3 concentrations increase until the age of 22 years, with a plateau being visible between 15 and 25 years. Determined by the high peripubertal peak in IGF-I, the peak in the IGF-I to IGFBP-3 ratio occurs already around the age of 15 years, with a slightly earlier and higher peak in females. Beyond the age of 60 years, IGFBP-3 concentrations remain higher in females, whereas IGF-I as well as the IGF-I to IGFBP-3 ratio remains significantly higher in males. CONCLUSIONS: We present an extensive set of assay-specific age- and sex-adjusted normative data for concentrations of IGFBP-3 and the molar IGF-I to IGFBP-3 ratio and demonstrate distinct sex specific differences across the life span.

The longitudinal association between weight change and health-related quality of life: the KORA S4/F4 cohort study.

OBJECTIVES: Despite the increasing importance of patient-centered perspectives, the impact of weight change on the health-related quality of life (HRQL) has remained unclear. This work aims to investigate this longitudinal relationship. METHODS: Data was collected from a population-based cohort study of 3,080 Germans. Anthropometrics and HRQL were assessed at baseline and after a 7-year follow-up period. Using linear regression the average change in HRQL scores was calculated among 5 mutually exclusive weight change groups. Multilevel growth modeling was conducted to differentiate between interpersonal (cross-sectional) and intrapersonal (longitudinal) associations between body mass index (BMI)/BMI change and HRQL. RESULTS: Heavy weight gain (≥10 % body weight) was associated with impairments in physical health among women (-2.82 points, CI: -4.29, -1.34) and obese men (-4.33 points, CI: -7.62, -1.04) and with improvements in mental health among women (+3.20 points, CI: +1.37, +5.02). Results from the multilevel models were consistent, showing negative associations between BMI change and physical health, positive associations between BMI change and mental health and a high degree of similarity between interpersonal and intrapersonal associations. CONCLUSIONS: Weight gain leads to clinically relevant impairments in physical health. More research is needed to clarify the antipodal effects of weight change on physical and mental health components.

Association between sleep disturbances and falls among the elderly: results from the German Cooperative Health Research in the Region of Augsburg-Age study.

OBJECTIVE: We aimed to examine the association between various sleep disturbances and falls among older individuals from the general population while considering the influence of age and dizziness. METHODS: Data were derived from the population-based cross-sectional KORA (Cooperative Health Research in the Region of Augsburg)-Age study, whereby information was conducted in standardized telephone interviews with 4127 men and women aged ⩾65years in 2008 and 2009. Unstratified and stratified (by age and dizziness) multivariable logistic regression model analyses were performed. RESULTS: The multivariable analysis showed a marginally significant association between trouble staying asleep and ⩾1 fall in the previous year (odds ratio [OR], 1.23 [95% confidence interval (CI), 1.01-1.50]). This association was more pronounced in participants older than the age of 75years (OR, 1.58 [95% CI, 1.16-2.16]) and in individuals without dizziness (OR, 1.35 [95% CI, 1.04-1.76]). There was no association between daytime sleepiness and falls in the fully-adjusted models, but the odds of falls in the previous year in individuals older than the age of 75years were significantly higher for individuals with difficulty falling asleep. Although sleep duration was not associated with falls in multivariable analyses when stratified by dizziness, sleep duration of 9h daily was significantly associated with higher odds of experiencing at least one fall in the previous year. CONCLUSIONS: Our study suggested that the positive relationship between a trend towards longer sleep duration, trouble falling and staying asleep, and falls is strongest in older individuals and in individuals who did not experience dizziness in the previous year.

The role of adiposity in cardiometabolic traits: a Mendelian randomization analysis.

BACKGROUND: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. METHODS AND FINDINGS: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n  =  198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p < 0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p < 0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p  =  0.001). CONCLUSIONS: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.

Metabolites associate with kidney function decline and incident chronic kidney disease in the general population.

BACKGROUND: Serum metabolites are associated cross-sectionally with kidney function in population-based studies. METHODS: Using flow injection and liquid chromatography tandem mass spectrometry methods, we examined longitudinal associations of baseline concentrations of 140 metabolites and their 19 460 ratios with kidney function decline and chronic kidney disease (CKD) incidence over 7 years in 1104 participants of the Cooperative Health Research in the Region of Augsburg S4/F4 study. RESULTS: Corrected for multiple testing, a significant association with annual change in the estimated glomerular filtration rate was observed for spermidine (P = 5.8 × 10(-7)) and two metabolite ratios, the phosphatidylcholine diacyl C42:5-to-phosphatidylcholine acyl-alkyl C36:0 ratio (P = 1.5 × 10(-6)) and the kynurenine-to-tryptophan ratio (P = 1.9 × 10(-6)). The kynurenine-to-tryptophan ratio was also associated with significantly higher incidence of CKD at the follow-up visit with an odds ratio of 1.36 per standard deviation increase; 95% confidence interval 1.11-1.66, P = 2.7 × 10(-3)). In separate analyses, the predictive ability of the metabolites was assessed: both the three significantly associated metabolite (ratios) as well as a panel of 35 metabolites selected from all metabolites in an unbiased fashion provided as much but not significantly more prognostic information than selected clinical predictors as judged by the area under the curve. CONCLUSIONS: Baseline serum concentrations of spermidine and two metabolite ratios were associated with kidney function change over subsequent years in the general population. In separate analyses, baseline serum metabolites were able to predict incident CKD to a similar but not better extent than selected clinical parameters. Our longitudinal findings provide a basis for targeted studies of certain metabolic pathways, e.g. tryptophan metabolism, and their relation to kidney function decline.

A genomewide association study of smoking relapse in four European population-based samples.

OBJECTIVES: Genomewide association studies (GWAS) have identified clear evidence of genetic markers for nicotine dependence. Other smoking phenotypes have been tested, but the results are less consistent. The tendency to relapse versus the ability to maintain long-term abstinence has received little attention in genetic studies; thus, our aim was to provide a better biological understanding of this phenotype through the identification of genetic loci associated with smoking relapse. METHODS: We carried out a GWAS on data from two European population-based collections, including a total of 835 cases (relapsers) and 990 controls (abstainers). Top-ranked findings from the discovery phase were tested for replication in two additional independent European population-based cohorts. RESULTS: Of the seven top markers from the discovery phase, none were consistently associated with smoking relapse across all samples and none reached genomewide significance. A single-nucleotide polymorphism rs1008509, within the Xylosyltransferase II (XYLT2) gene, was suggestively associated with smoking relapse in the discovery phase (ß=-0.504; P=5.6E-06) and in the first replication sample (ALSPAC) (ß=-0.27; P=0.004; n=1932), but not in the second sample (KORA) (ß=0.19; P=0.138; n=912). We failed to identify an association between loci implicated previously in other smoking phenotypes and smoking relapse. CONCLUSION: Although no genomewide significant findings emerged from this study, we found that loci implicated in other smoking phenotypes were not associated with smoking relapse, which suggests that the neurobiology of smoking relapse and long-term abstinence may be distinct from biological mechanisms implicated in the development of nicotine dependence.

Reproductive factors and its association with peripheral arterial disease in women aged 52-81 years: the KORA F4 study.

OBJECTIVE: Sex differences in the onset of cardiovascular disease disappear in the postmenopause, suggesting that reproductive factors could be influential. The aim of the present study was to examine the possible association between reproductive parameters and peripheral arterial disease (PAD) in a female population-based sample. METHODS: In this cross-sectional study data of 887 women aged 52-81 years participating in the population-based KORA F4 study (conducted in 2006-2008) was analyzed. Reproductive parameters were obtained by standardized interviews. PAD was assessed by measuring noninvasively the ankle-brachial index and using a cut-off value of 0.9 and by assessing the presence of claudication by the Edinburgh questionnaire. RESULTS: In multivariable logistic regression analyses later age at menarche (>15 years) compared to age at menarche between 12 and 15 years was significantly associated with about half the probability for PAD (OR = 0.48; 95%CI 0.24-0.98). The presence of hot flashes was positively associated with PAD (OR = 2.09; 95%CI 1.11-3.92). Further reproductive parameters, such as parity, age at menopause, time since menopause, duration of fertility, ever use or current use of hormone replacement therapy, ever use of oral contraceptives, history of hysterectomy, bilateral oophorectomy and depressive mood in relation to menopausal transition showed no significant association with PAD. CONCLUSIONS: Later age at menarche was inversely related to PAD and the presence of hot flashes was associated with an increased presence of PAD. Prospective population-based studies in women are needed to assess the impact of reproductive parameters on the development of PAD and subsequently cardiovascular disease.

Meta-analysis of genome-wide association studies in five cohorts reveals common variants in RBFOX1, a regulator of tissue-specific splicing, associated with refractive error.

Visual refractive errors (REs) are complex genetic traits with a largely unknown etiology. To date, genome-wide association studies (GWASs) of moderate size have identified several novel risk markers for RE, measured here as mean spherical equivalent (MSE). We performed a GWAS using a total of 7280 samples from five cohorts: the Age-Related Eye Disease Study (AREDS); the KORA study ('Cooperative Health Research in the Region of Augsburg'); the Framingham Eye Study (FES); the Ogliastra Genetic Park-Talana (OGP-Talana) Study and the Multiethnic Study of Atherosclerosis (MESA). Genotyping was performed on Illumina and Affymetrix platforms with additional markers imputed to the HapMap II reference panel. We identified a new genome-wide significant locus on chromosome 16 (rs10500355, P = 3.9 × 10(-9)) in a combined discovery and replication set (26 953 samples). This single nucleotide polymorphism (SNP) is located within the RBFOX1 gene which is a neuron-specific splicing factor regulating a wide range of alternative splicing events implicated in neuronal development and maturation, including transcription factors, other splicing factors and synaptic proteins.

Physical activity is inversely associated with multimorbidity in elderly men: results from the KORA-Age Augsburg Study.

OBJECTIVE: Physical activity is suggested to play a key role in the prevention of several chronic diseases. However, data on the association between physical activity and multimorbidity are lacking. METHODS: Using data from 1007 men and women aged 65-94 years who participated in the population-based KORA (Cooperative Health Research in the Region of Augsburg)-Age project conducted in Augsburg/Germany and two adjacent counties in 2008/09, 13 chronic conditions were identified, and physical activity scores were calculated based on the self-reported physical activity scale for the elderly (PASE). Multivariable sex-specific logistic regression was applied to determine the association of the continuous physical activity score with multimorbidity (≥ 2 out of 13 diseases). RESULTS: Physical activity (mean PASE score±SD) was higher in men (125.1 ± 59.2) than in women (112.2 ± 49.2). Among men, the odds ratio (OR) for multimorbidity was 0.73 (95% CI: 0.60-0.90) for a 1 standard deviation increase of the PASE score. No significant results could be observed for women (OR: 1.05; 95% CI: 0.83-1.33). CONCLUSION: We demonstrated an inverse association between physical activity and multimorbidity among men. Further prospective studies have to confirm the temporality of effects.

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia.

Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

High serum thyrotropin levels are associated with current but not with incident hypertension.

BACKGROUND: Recent data from a population-based study in children and adolescents suggest that serum thyrotropin (TSH) levels are associated with arterial blood pressure and hypertension. These results are in agreement with some but not all population-based studies in adults. Discrepancies in results might be explained by drug intake, different iodine supplies, and sizes of populations investigated. In addition, it is not clear whether an association between TSH and hypertension exists longitudinally or only cross-sectionally. Thus, our aim was to investigate cross-sectional and longitudinal associations between thyroid function and arterial blood pressure in a large consortium of cohort studies in adults. METHODS: Data from five population-based studies were pooled resulting in 17,023 individuals being available for cross-sectional and 10,048 individuals for longitudinal analyses. Associations of baseline TSH with baseline blood pressure or hypertension were analyzed by multivariable median or logistic regression models. Multivariable median or Poisson regression models were used to investigate associations of baseline TSH with five-year change in arterial blood pressure or incident hypertension. RESULTS: There was a cross-sectional positive association of TSH with arterial blood pressure (p<0.001) and hypertension (odds ratio [OR]=1.76 [confidence interval (CI) 1.24-2.50], p=0.002). Likewise, hypothyroidism was associated with systolic (ß=1.1 [CI 0.1-2.1], p=0.040) and diastolic blood pressure (ß=1.4 [CI 0.7-2.0], p<0.001). TSH, however, was not consistently associated with a five-year change in blood pressure or incident hypertension. CONCLUSIONS: High serum TSH levels were associated with current hypertension and blood pressure but not with a five-year change in blood pressure and incident hypertension. This argues for only a short-term effect of thyroid hormone levels on arterial blood pressure or a spurious association that needs further evaluation in population-based studies.